Pluripotent stem cell research has developed over the last fifty years from the study of embryonic development to a multifaceted discipline that encompasses development, epigenetics, reprogramming, cell therapy, disease modeling and chemical and drug screening. The idea of patient-specific therapies and disease modeling using human pluripotent stem cells has been the theoretical golden-egg of the field since the generation of human embryonic stem cells. With the advent of induced pluripotent stem cells (PSCs), the ability to generate patient-specific cells for therapeutic use, to model disease progression and to test drugs on disease relevant cells moved a large step closer to reality. While there still is a long way to go before the results of PSC research is found in the clinic or in the pharmacy, recent developments have demonstrated that it is possible to generate patient-specific pluripotent cells which can differentiate into disease relevant cell types, are amenable to gene correction, can phenocopy molecular and functional disease characteristics, at least in vitro, and can be used to validate the efficacy of therapeutic compounds. This review will cover recent developments in the generation and manipulation of pluripotent stem cells with a focus on the use of pluripotent stem cells for disease modeling and therapeutic drug screening. In addition, the latest developments in somatic cell reprogramming will also be discussed.